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Céline Parmentier, Delilah F G Hendriks, Bruno Heyd, Philippe Bachellier, Magnus Ingelman-Sundberg, Lysiane Richert
Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in response towards cholestatic hepatotoxins after short-term (48-72 h) and long-term repeated exposures (14 days). Cholestatic liabilities were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid (BA) mixture...
June 15, 2018: Toxicology Letters
Elyse J McGlumphy, Jordan A Margo, Moulaye Haidara, Clayton H Brown, Caroline K Hoover, Wuqaas M Munir
PURPOSE: Corneal endothelial cell density (ECD) is an important measure for determining suitability for transplantation. Although age has been correlated with ECD, the impact of sex and ethnicity is unclear. METHODS: Corneal donor information from SightLife Eye Bank was collected between 2012 and 2016. Tests of association were adjusted for covariates using linear regression including age, race, and sex. "Unsuitable for transplantation" was a label assigned to specimens with extensive cell dropout, ECD <2000 cells/mm, and poor cell morphology...
June 14, 2018: Cornea
Siamak Yaghobee, Nina Rouzmeh, Hoori Aslroosta, Sanaz Mahmoodi, Afshin Khorsand, Mohamad Javad Kharrazifard
Free gingival grafting, the most predictable technique to increase the keratinized gingiva, leaves an open wound on the palate and the resulting discomfort during the healing phase is a significant concern. This study was intended to evaluate the effect of topical erythropoietin on healing of the donor site. Twelve patients lacking an attached gingiva at two sites in the mandible were included. In the test group, 1 mL of gel containing erythropoietin at a concentration of 4,000 IU mL-1 was applied to the donor site, whereas the control group was treated with 2 mL of the gel alone...
June 11, 2018: Brazilian Oral Research
Yun Wang, Taro Masaki, Sikandar G Khan, Deborah Tamura, Christiane Kuschal, Megan Rogers, John J DiGiovanna, Kenneth H Kraemer
Recent findings of mosaicism (DNA sequence variation) challenge the dogma that each person has a stable genetic constitution. Copy number variations, point mutations and chromosome abnormalities in normal or diseased tissues have been described. We studied normal skin mosaicism of a single nucleotide polymorphism (SNP) [rs1426654, p.Thr111Ala] in SLC24A5, an ion transporter gene. This SNP is unusual in that more than 90% of people of European descent have homozygous germline A/A alleles, while more than 90% of East Asians and Blacks have homozygous germline G/G alleles...
2018: PloS One
Cheng-Zhou Mao, Li Zheng, Yi-Min Zhou, Hai-Yan Wu, Jing-Bo Xia, Chi-Qian Liang, Xiao-Fang Guo, Wen-Tao Peng, Hui Zhao, Wei-Bin Cai, Soo-Ki Kim, Kyu-Sang Park, Dong-Qing Cai, Xu-Feng Qi
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system has emerged as a powerful tool for knock-in of DNA fragments via donor plasmid and homology-independent DNA repair mechanism; however, conventional integration includes unnecessary plasmid backbone and may result in the unfaithful expression of the modified endogenous genes. Here, we report an efficient and precise CRISPR/Cas9-mediated integration strategy using a donor plasmid that harbors 2 of the same cleavage sites that flank the cassette at both sides...
June 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Pedro Ventura-Aguiar, Joana Ferrer, Ignacio Revuelta, David Paredes, Erika de Sousa-Amorim, Jordi Rovira, Enric Esmatjes, Juan Carlos Garcia-Valdecasas, Josep M Campistol, Federico Oppenheimer, Fritz Diekmann, Maria José Ricart
Background: Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed. Methods: We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference...
June 8, 2018: Nephrology, Dialysis, Transplantation
Oscar Ramos-Campoy, Rainiero Ávila-Polo, Oriol Grau-Rivera, Anna Antonell, Jordi Clarimón, Ricardo Rojas-García, Sara Charif, Veronica Santiago-Valera, Isabel Hernandez, Miquel Aguilar, Consuelo Almenar, Dolores Lopez-Villegas, Lorena Bajo, Pau Pastor, Julie Van der Zee, Albert Lladó, Raquel Sanchez-Valle, Ellen Gelpi
The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI)...
June 7, 2018: Journal of Neuropathology and Experimental Neurology
Jacqueline M Smits, Michel De Pauw, Uwe Schulz, Johan Van Cleemput, Philip Raake, Ivan Knezevic, Kadir Caliskan, Zeljko Sutlic, Christoph Knosalla, Felix Schoenrath, Zoltan Szabolcs, Jens Gottlieb, Christian Hagl, Andreas Doesch, Davor Baric, Igor Rudez, Agita Strelniece, Erwin De Vries, Dave Green, Undine Samuel, Davor Milicic, Istvan Hartyanszky, Michael Berchtold-Herz, P Christian Schulze, Friedrich Mohr, Bruno Meiser, Axel Haverich, Hermann Reichenspurner, Jan Gummert, Guenter Laufer, Andreas Zuckermann
Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within one week after heart transplantation (HTX) are indicated for high urgency (HU) listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981- 2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischemia time, recipient diagnose, urgency status and era...
June 8, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Xingbin Chen, Xiaomei Sun, Leiming Dong, Shougong Zhang
Pollination dynamics highly determines the genetic quality of seed orchard crops. However, there is less research about the effect of mating patterns on seed productivity of orchard crops. So far, clonal seed orchards have been producing genetically improved seedlings used for most Japanese larch (Larix kaempferi (Lamb.) Carr.) plantations in China. In the present study, a total of 17 highly variable simple sequence repeat (SSR) markers were used for genotyping a progeny trial population consisting of 647 open-pollinated progenies germinated from seeds which were collected from 63 maternal clones with 140 potential paternal clones in a Japanese larch clonal seed orchard in China...
June 4, 2018: Science China. Life Sciences
Y Goto, N Shirahama, S Sasaki, R Kawahara, H Sakai, H Ishikawa, T Hisaka, T Ogata, M Yasunaga, Y Akagi, H Tanaka, K Okuda
BACKGROUND: Some literature has reported on endovascular treatment for very early hepatic artery stenosis (HAS; within 2 weeks after liver transplantation, and has deemed endovascular treatment to be a contraindication because out of serious complications associated with the procedure. We report on 2 cases of very early HAS successfully treated with endovascular treatment after living-donor liver transplantation (LDLT). CASE 1: A 54-year-old woman underwent LDLT with a left liver graft...
June 2018: Transplantation Proceedings
Shawn Meyers, Jessica Shih, Jon O Neher, Sarah Safranek
Fecal microbial transplant (fmt) is reasonably safe and effective. In patients who have had multiple Clostridium difficile infections (CDIs), fecal microbial transplant (FMT) results in a 65% to 80% cure rate with one treatment and 90% to 95% cure rate with repeated treatments compared with a 25% to 27% cure rate for antibiotics (strength of recommendation [SOR]: B, small open-label randomized controlled trials [RCTs]). Fresh and frozen donor feces, administered by either nasogastric tube or colonoscope, produce equal results (SOR B, RCTs)...
June 2018: Journal of Family Practice
J J Windig, H P Doekes
Outcrossing should reduce inbreeding levels and associated negative effects in highly inbred populations. In this study, we investigated the effectiveness of different outcrossing schemes using computer simulations. The inbreeding rate estimated for a 25-year period of 2.1% per generation in a highly inbred dog breed reduced to 1.8% when a single litter was produced by an outcross without backcrosses. To reduce the inbreeding rate below 1%, more than eight of the 14 litters born yearly in the recipient breed had to be outcrossed...
June 2018: Journal of Animal Breeding and Genetics, Zeitschrift Für Tierzüchtung und Züchtungsbiologie
Norman Lu, Chih Chieh Kung, Jia Yu Huang, Yu Xuan Li, Chung Kuang Yang, Yuh Sheng Wen, Ling Kang Liu
The polyfluorinated title compounds, [MBr2 (C18 H16 F8 N2 O2 )] or [4,4'-(HCF2 CF2 CH2 OCH2 )2 -2,2'-bpy]MBr2 , (1) (M = Pd and bpy is bipyridine) and (2) (M = Pt), have -CH(α)2 OCH(β)2 CF2 CF2 H side chains with methylene H-atom donors at the α and β sites, and methine H-atom donors at the terminal sites, in addition to aromatic H-atom donors. In contrast to the original expectation of isomorphous structures, (1) crystallizes in the space group C2/c and (2) in P21 /n, with similar unit-cell volumes and Z = 4...
June 1, 2018: Acta Crystallographica. Section C, Structural Chemistry
A B Lara, C Caballo, M D Sicilia, S Rubio
Halogen bonding (XB), a highly energetic and directional interaction, is here proposed as a new mechanism to increase solute solubilisation in solvent extractions. The approach is illustrated by the extraction of hexabromocyclododecane (HBCD) enantiomers in soils and sediments using supramolecular solvents (SUPRAS) containing XB donors in their structure. SUPRAS consisting of inverted hexagonal aggregates of decanoic acid, synthesized by water-induced coacervation of the amphiphile in tetrahydrofuran (THF), were explored for this purpose...
October 16, 2018: Analytica Chimica Acta
Takayuki Arazoe, Akihiko Kondo, Keiji Nishida
Since the emergence of programmable RNA-guided nucleases based on Clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein (Cas) systems, genome editing technologies have become a simplified and versatile tool for genome editing in various organisms and cell types. Although genome editing enables efficient genome manipulations, such as gene disruptions, gene knockins, and chromosomal translocations via DNA double-strand break (DSB) repair in eukaryotes, DSBs induced by the CRISPR/Cas system are lethal or severely toxic to many microorganisms...
June 3, 2018: Biotechnology Journal
Kristiaan J van der Gaag, Rick H de Leeuw, Jeroen F J Laros, Johan T den Dunnen, Peter de Knijff
Since two decades, short tandem repeats (STRs) are the preferred markers for human identification, routinely analysed by fragment length analysis. Here we present a novel set of short hypervariable autosomal microhaplotypes (MH) that have four or more SNPs in a span of less than 70 nucleotides (nt). These MHs display a discriminating power approaching that of STRs and provide a powerful alternative for the analysis;1;is of forensic samples that are problematic when the STR fragment size range exceeds the integrity range of severely degraded DNA or when multiple donors contribute to an evidentiary stain and STR stutter artefacts complicate profile interpretation...
May 22, 2018: Forensic Science International. Genetics
Caroline Y Kuo, Joseph D Long, Beatriz Campo-Fernandez, Satiro de Oliveira, Aaron R Cooper, Zulema Romero, Megan D Hoban, Alok V Joglekar, Georgia R Lill, Michael L Kaufman, Sorel Fitz-Gibbon, Xiaoyan Wang, Roger P Hollis, Donald B Kohn
X-linked hyper-immunoglobulin M (hyper-IgM) syndrome (XHIM) is a primary immunodeficiency due to mutations in CD40 ligand that affect immunoglobulin class-switch recombination and somatic hypermutation. The disease is amenable to gene therapy using retroviral vectors, but dysregulated gene expression results in abnormal lymphoproliferation in mouse models, highlighting the need for alternative strategies. Here, we demonstrate the ability of both the transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) platforms to efficiently drive integration of a normal copy of the CD40L cDNA delivered by Adeno-Associated Virus...
May 29, 2018: Cell Reports
Juan-Juan Luo, Wan-Ping Bian, Yi Liu, Hai-Yang Huang, Qian Yin, Xiao-Jun Yang, De-Sheng Pei
Numerous feasible methods for inserting large fragments of exogenous DNA sequences into the zebrafish genome have been developed, as has genome editing technology using programmable nucleases. However, the coding sequences of targeted endogenous genes are disrupted, and the expression patterns of inserted exogenous genes cannot completely recapitulate those of endogenous genes. Here we describe the establishment of a novel strategy for endogenous promoter-driven and microhomology-mediated end-joining-dependent integration of a donor vector using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9...
May 29, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Franco Grimaldi, Fabio Vescini, Veronica Tonelli, Cinzia Pistis, Elda Kara, Vincenzo Triggiani, Elio Tonutti, Francesco Curcio, Martina Fabris
BACKGROUND AND OBJECTIVE: BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs). METHODS: The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas)...
May 28, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Jiyue Bai, Yongqing Xu, Xiaoqing He, Chuan Li, Shuai Liu, Liang Li
Objective: To compare the biomechanical characteristics of self-made nickel-titanium shape memory alloy stepped plate with calcaneal plate and cannulated compression screws in fixing calcaneal osteotomy. Methods: Calcaneal osteotomy was operated on 6 fresh-frozen lower limbs collected from donors. Then three kinds of fixation materials were applied in random, including the self-made nickel-titanium shape memory alloy stepped plate (group A), calcaneal plate (group B), and cannulated compression screws (group C)...
February 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
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